Travelling on the potential energy surfaces of carbohydrates: Comparative application of an exhaustive systematic conformational search with an heuristic search

The calculated ensembles found by a heuristic conformational search algorithm, CICADA, for three small carbohydrates, ethyl β-lactoside, methyl α-d-galactoside, and methyl β-d-galactoside, are evaluated in terms of their ability to reproduce time-averaged optical rotation and NMR data. A unique dynamic model for methyl β-d-galactoside has been obtained by fitting experimental NOESY volumes to the theoretical ones elaborated from the CICADA ensemble internuclear distances with the model-free formalism. In the case of ethyl β-lactoside, the CICADA ensemble is compared to that of an exhaustive systematic grid-search method. The CICADA algorithm proved to be a very efficient method to find most of the important minima on even very complex potential energy surfaces, and the spectral quality of the CICADA ensemble was found to be of equal quality, if not superior, to that of the exhaustive systematic grid-search method. The CICADA algorithm has several advantages over other conformational search algorithms: (1) It has polynomial dependence of dimensions on computer time in contrast to the grid search, which has exponential dependence, (2) the conformations found are free of artificial harmonic constraint potentials, (3) it passes all barriers amongst families of conformations on conformational hypersurface but spends almost all its time in the essential highly populated areas, (4) the inherent properties of the algorithm make rigorous minimization criteria superfluous and provide good convergence behavior, and (5) as an important spin-off, it provides low-energy interconversion pathways that can, amongst others, be used for estimating adiabatic rotational barriers.